evaluation of left ventricular diastolic function by the ... · medicine.3 this article will review...
TRANSCRIPT
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Accepted Manuscript
Evaluation of Left Ventricular Diastolic Function by the Intensivist
Yonatan Y. Greenstein, MD, Paul H. Mayo, MD FCCP
PII: S0012-3692(17)33045-3
DOI: 10.1016/j.chest.2017.10.032
Reference: CHEST 1418
To appear in: CHEST
Received Date: 17 September 2017
Revised Date: 17 October 2017
Accepted Date: 19 October 2017
Please cite this article as: Greenstein YY, Mayo PH, Evaluation of Left Ventricular Diastolic Function bythe Intensivist, CHEST (2017), doi: 10.1016/j.chest.2017.10.032.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service toour customers we are providing this early version of the manuscript. The manuscript will undergocopyediting, typesetting, and review of the resulting proof before it is published in its final form. Pleasenote that during the production process errors may be discovered which could affect the content, and alllegal disclaimers that apply to the journal pertain.
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Text Word Count: 3,888
Abstract Word Count: 78
Title: Evaluation of Left Ventricular Diastolic Function by the Intensivist
Author List
Yonatan Y. Greenstein, MD (corresponding author)
Rutgers – New Jersey Medical School
University Hospital Building
Room I-354
Newark, NJ 07103
Paul H. Mayo, MD FCCP
Hofstra Northwell School of Medicine
410 Lakeville Road, Suite 107
New Hyde Park, NY 11040
Summary conflict of interest statements: Authors YYG and PHM have no conflicts of interest pertaining
to this manuscript.
Funding information: none
Abbreviations
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LV – Left ventricle
ACCE – Advanced critical care echocardiography
LAP – Left atrial pressure
MV – Mitral valve
ASE – American Society of Echocardiography
EACI – European Association of Cardiovascular Imaging
2D – Two-dimensional
PW – Pulsed wave
CW – Continuous wave
TDI – Tissue Doppler imaging
CFD – Color flow Doppler
LA – Left atrium
AP4 – Apical four
TTE – Transthoracic echocardiography
TEE – Transeosphageal echocardiography
TR – Tricuspid regurgitation
e’ – Peak velocity of the mitral valve annulus
LVEF – Left ventricular ejection fraction
MR – Mitral regurgitation
Abstract
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The assessment of left ventricular diastolic function is an important element of advanced critical care
echocardiography. Standard methods of evaluating diastolic function that are routinely performed on an
elective basis in the cardiology echocardiography laboratory may be difficult to apply in the critical care
unit. In this article, we review methods of measuring diastolic function with echocardiography that are
of relevance to the intensivist and present two options for measurement: the standard cardiology
method and a simplified approach.
Introduction
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Competence in assessing left ventricular (LV) diastolic function is a required element of advanced critical
care echocardiography (ACCE) as defined in the American College of Chest Physicians / Société de
Reanimation de Langue Francaise Statement on Competence in Critical Care Ultrasonography1 and in
the International Statement on Training in ACCE.2
It follows that the intensivist with interest in
developing competence in ACCE seeks to become skilled at the evaluation of diastolic function at a level
similar to their cardiology colleague with emphasis on clinical applications that relate to critical care
medicine.3 This article will review the use of ACCE for evaluation of LV diastolic function, and serves as a
companion article to the two-part series on the subject that was previously featured in CHEST.4,5
Throughout this article, diastolic function will refer to left sided cardiac diastolic function.
Relevance of Left Ventricular Diastolic Function to the Critical Care Clinician
A regular challenge to the frontline intensivist is the patient on ventilatory support with bilateral
opacities on chest radiography and diffuse bilateral B-lines on lung ultrasonography. Does the patient
have lung disease due to an elevation in left atrial pressure (LAP), due to primary lung injury (e.g. acute
respiratory distress syndrome), or do they have both? Absent the ability to answer the question with a
pulmonary artery catheter, echocardiography allows the intensivist to estimate LAP, which is a key
component in the hemodynamic evaluation of the patient. While identification of an elevation in LAP in
association with respiratory failure has major therapeutic implications, it has other uses as well. A new
elevation of LAP during a spontaneous breathing trial indicates a load related failure of the trial with the
possibility of therapeutic intervention.6,7
The finding of an elevation of LAP in any circumstance requires
consideration of the mechanism for the elevation. Our opinion is that the estimation of LAP is a primary
application of interest to the intensivist in evaluating diastolic function.
In addition to estimation of LAP, echocardiography allows the intensivist to identify normal diastolic
function and to categorize the grade of diastolic dysfunction when it is present. Diastolic dysfunction in
septic patients occurs with a prevalence of 20% to 57%8-11
and is associated with increased
mortality.9,10,12-15
Diastolic dysfunction has also been shown to be associated with mechanical ventilation
liberation outcomes, and its presence is an independent risk factor for liberation failure.16-18
The
presence of diastolic dysfunction in the critically ill patient who is hemodynamically stable may not
result in any immediate change in management; however, it cautions the intensivist of potential
problems. For example, its presence may predict the risk of developing cardiogenic pulmonary edema
with changes in cardiac loading conditions such as volume resuscitation, hypertension, tachycardia, or
inadequate dialysis treatment. The patient with diastolic dysfunction may be at increased risk for
hypotension related to hypovolemia and/or tachycardia.
Diastolic Function
Diastole is the interval of the cardiac cycle between the closure of the aortic valve and the closure of the
mitral valve (MV). This interval consists of four phases: isovolumic relaxation, early diastolic filling,
diastasis, and late diastolic filling (Figure 1). There are numerous factors that influence diastolic function
including ventricular relaxation, ventricular compliance, ventricular recoil, ventricular suction effect,
atrial compliance, atrial contractility, and mitral valve function. Added to these are the effects of
pericardial pressure, intrathoracic pressure, right ventricular function through interventricular
dependence, and LV systolic function with its derivatives. To further complicate matters, loading
conditions that influence diastolic function change rapidly in critical illness. Echocardiography allows the
physician to see and measure multiple indices of diastolic function noninvasively while maintaining good
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concordance with the gold standard, invasive hemodynamic monitoring.19-21
We will limit the discussion
to the elements of diastolic function that are addressed in the standard consultative cardiology
echocardiography examination to estimate LAP and to grade diastolic function.
The Cardiology Approach to Evaluation of Diastolic Function
As a reflection of the enduring interest by cardiologists in the assessment of diastolic function, a search
of PubMed using the key words “echocardiography” and “diastolic function” yields 22,310 citations. In
view of the increasing complexity of the subject, in 2009 the American Society of Echocardiography
(ASE) issued a guideline document titled Recommendations for the Evaluation of Left Ventricular
Diastolic Function by Echocardiography.22
In addition to providing a comprehensive review of the
subject, the document presented three figures that described an algorithmic approach to the evaluation
of diastolic function. These allowed estimation of LAP (elevated or not elevated without specific
numerical value) and classification of diastolic function as either normal diastolic function or into 3
separate grades of dysfunction (I, II, III). While the 2009 ASE algorithms brought order to a complex field,
intensivists have had difficulty using them in frontline practice in the intensive care unit. The algorithm
required measurement of a variety of parameters that could not be readily obtained in the critically ill
patient. Patient related factors (obesity, edema, failure of ability to position the patient, surgical
dressings etc.) as well as time constraints characteristic of intensivist performed ACCE regularly
combined to yield indeterminate results when applying the ASE recommendations.23
In 2016, the ASE and the European Association of Cardiovascular Imaging (EACI) issued a guideline
document titled Recommendations for the Evaluation of Left Ventricular Diastolic Function by
Echocardiography: An Update from the American Society of Echocardiography and the European
Association of Cardiovascular Imaging.24
This document is required reading for all intensivists who are
interested in ACCE, as it offers a comprehensive review of the field. It presents a revision of the
algorithms for estimating LAP and for grading diastolic dysfunction. The two new algorithms are
summarized and will be discussed in detail in a later section (Figure 2A-B). The new ASE/EACI guidelines
represent a welcome simplification from the previous standard. The question is whether the ACCE
community can apply the new algorithms in frontline practice. Of note, the ASE/EACI algorithms are
based upon expert consensus and have not been further validated.
The Echocardiographic Assessment of Diastolic Function
Equipment
The echocardiographic assessment of diastolic function requires a machine capable of good quality two-
dimensional (2D) ultrasonography with full Doppler capability: pulsed wave (PW) Doppler, continuous
wave (CW) Doppler, tissue Doppler imaging (TDI), and color flow Doppler (CFD). Good quality Doppler
measurements may be obtained using a wide variety of the small portable echocardiography machines
that are common in critical care units. Large cardiology type echocardiography machines are not
required.
Doppler Measurements
Measurement of diastolic function requires knowledge of Doppler physics and signal acquisition. Due to
space constraints, this article will not review Doppler physics in any detail. The reader is directed to
standard texts on echocardiography for full discussion of Doppler physics.25,26
Table 1 summarizes
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important aspects of the different types of Doppler ultrasonography that are relevant to measurement
of diastolic function.
A major difference between consultative cardiology echocardiography and ACCE is that that the
intensivist is personally responsible for all aspects of image acquisition, image interpretation, and clinical
applications at the point of care. Skill at acquisition of Doppler signals is a key component of
competence for the intensivist.
Mitral Valve Inflow
Doppler ultrasonography allows the intensivist to visualize the phases of diastole. Following isovolumic
relaxation, the MV opens with rapid acceleration of blood flow from the left atrium (LA) to the LV. This
results in the E wave velocity curve. The peak velocity of the E wave is a required measurement for the
assessment of diastolic function. After diastasis, which is the period of minimal flow after early diastolic
filling; atrial contraction occurs, resulting in the late diastolic A wave velocity curve. This is a required
measurement for the assessment of diastolic function. The peak E wave velocity and peak A wave
velocity are measured from the same image (Figure 3). This is accomplished by obtaining an apical 4
(AP4) chamber view of the heart and placing a PW Doppler echocardiography sample volume in the LV
cavity between the tips of the mitral valve leaflets (Video 1). With transthoracic echocardiography (TTE),
the flow of blood into the LV cavity on the AP4 chamber view is towards the transducer, so the E and the
A waves are positive deflections. With transesophageal echocardiography (TEE) using the mid-
esophageal four chamber view, the flow of blood is away from the transducer and the deflections are
negative. Normal values for young healthy subjects for these measurements are presented in Table 2.
The normative values for elderly patients are different, with the peak E wave velocity being somewhat
lower. Patients with atrial fibrillation do not have a measurable A wave. Patients with tachycardia or
prolonged atrial-ventricular nodal conduction may have fusion of the E wave and A wave, rendering
measurement of the peak A wave velocity inaccurate.
The ASE/EACI algorithm for measurement of LV diastolic function algorithm requires, in some
circumstances, measurement of the tricuspid regurgitation (TR) jet velocity when measurement of peak
E and A wave velocity is not sufficient to categorize diastolic function. Peak TR velocity is measured from
the right ventricular inflow view, the parasternal short-axis view at the level of the aortic and tricuspid
valve, the AP4 chamber view (Figure 4), and/or the subcostal long axis view using CW Doppler. In
recognition of the angle dependence with CW, the highest recorded velocity is the relevant velocity. The
TR jet may be eccentric in pattern, so a single velocity measurement is not sufficient. The CFD sample
box is useful for placement of the CW interrogation line.
Tissue Doppler Imaging
Tissue Doppler Imaging allows for the analysis of myocardial velocities at specific locations throughout
the cardiac cycle. For application of the ASE/EACI algorithm, the intensivist measures myocardial
velocities along the longitudinal plane of mitral annular movement during diastole from the AP4
chamber view of the heart (or the mid-esophageal 4 chamber view with TEE). When measured in this
way, the myocardial velocity reflects changes in the length of the myocardial fibers along a longitudinal
plane. Tissue Doppler imaging of the mitral annulus results in two velocity curves occurring in early and
late diastole. The ASE/EACI algorithm requires TDI measurement of the peak velocity of the mitral valve
annulus (e’). The e’ TDI velocity reflects the rate of LV relaxation during diastole and is less load
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dependent than conventional Doppler parameters.27,28
This peak velocity is measured by obtaining an
AP4 chamber view of the heart with placement of the TDI sample volume on the mitral annulus (Figure
5, Video 2). The lateral or septal annulus can be used for this measurement; the normative values differ,
with septal velocities being lower and more reproducible than lateral velocities (Table 2).25
Care is taken
to ensure that an AP4 chamber view is used as an apical 5 chamber view will result in inaccurate
measurements due to the presence of the left ventricular outflow tract. As opposed to the E and A wave
velocities, the e’ velocity is directed away from the transducer during TTE and is represented by a
negative deflection. If measuring the e’ velocity with TEE, it is represented by a positive deflection.
There are a variety of other measurements that can be made from mitral inflow such as isovolumic
relaxation time, E wave deceleration time, and duration of the A wave which, when combined with
Doppler based analysis of pulmonary venous inflow, have been used to assess LV diastolic function.
While these measurements are not part of the new ASE/EACI algorithm, we recommend that the
intensivist with interest in ACCE review their basis so as to have a comprehensive background in the
field.
Measurements Derived from 2D Echocardiography
While Doppler measurements dominate assessment of LV diastolic function, 2D echocardiography
findings are relevant. In the setting of normal LV systolic function and normal mitral valve function, an
enlarged LA is a marker of diastolic dysfunction. This rule particularly applies when there is an increase
in LV wall thickness (e.g. hypertrophy, infiltrative myocardial disease). The intensivist performing
bedside ACCE can assess the patient for LA enlargement qualitatively. This is best accomplished from the
parasternal long axis view; LA enlargement is present if the transverse diameter of the LA is greater than
the diameter of the proximal ascending aorta. A simple quantitative method of estimating LA size is by
using the traditional M-mode technique, whereby the M-mode scan line is adjusted to pass through the
aortic valve to measure the greatest systolic dimension of the LA. While this has the advantage of
simplicity, its disadvantage is that it uses a single linear measurement to represent a complex three-
dimensional structure. In consultative cardiology echocardiography, LA volume is measured by using the
disk summation method, whereby two orthogonal views of the LA in the AP4 chamber view and the
apical 2 chamber view are analyzed. The upper limit of normal for LA volume is 34 mL/m2.29 This
measurement is time consuming and difficult to perform given the challenges of imaging the critically ill
patient. The reader is referred to the 2015 ASE/EACI guidelines for more details.29
The ASE and the EACI Guidelines for the Evaluation of Diastolic Function by Echocardiography
In 2016, the ASE/EACI revised their 2009 guidelines to simplify the assessment of diastolic function by
echocardiography.22,24
This algorithm is required reading for the intensivist with interest in ACCE. For
patients with normal left ventricular ejection fraction (LVEF), the guidelines recommend four
measurements with cutoffs denoting an abnormal finding for identifying diastolic dysfunction: 1) e’
velocity (septal e’ < 7 cm/sec; lateral e’ < 10 cm/sec; 2) average E/e’ ratio > 14 (lateral E/e; > 13, septal
E/e’ > 15); 3) LA volume index > 34 mL/m2; 4) peak tricuspid regurgitation velocity < 2.8 m/s. In patients
with normal LVEF, the guidelines define diastolic dysfunction if three or more measurements are
abnormal (Figure 2A). Less than three abnormal measurements establish normal diastolic function,
three or more abnormal measurements establishes diastolic dysfunction, and two abnormal
measurements is an indeterminate result. If diastolic dysfunction is present, the degree of diastolic
dysfunction can then be determined by following an additional algorithm (Figure 2B). For patients with a
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depressed LVEF, the second algorithm is used with addition of the E/A ratio (Figure 2B). The 2016
ASE/EACI guidelines define normal LVEF ≥ 50%, indicating that an LVEF < 50% represents depressed
systolic function.
In addition to classifying diastolic function, the algorithm can be used to determine the presence or
absence of an elevated LAP (Figure 2B). A normal LAP is defined by E/A ≤ 0.8 and E ≤ 50 cm/s. If E/A ≥ 2,
then LAP is elevated. For patients whose mitral inflow measurements fall between these values, the
average E/e’, TR velocity, and LA can be measured. If ≥ 2 are abnormal, the patient has increased LAP; if
< 2 measurements are abnormal the LAP is indeterminate.
Limitations of the ASE algorithm
For both the intensivist and cardiologist, certain conditions exclude the use of the algorithm. Mitral
annular calcification and basal segmental wall motion abnormalities invalidate the measurement of
mitral valve annular e’. Mitral stenosis and significant mitral regurgitation (MR) invalidate the
measurement of mitral inflow velocities. Tachycardia and prolonged atrio-ventricular nodal conduction
may lead to fusion of the E and A waves resulting in inaccurate assessment of A wave velocities. Atrial
fibrillation with variable RR intervals and absence of A waves makes it difficult to apply the algorithm.
Alternative methods for evaluating diastolic dysfunction can be found in the ASE/EACI guideline
document.24
The assessment of LAP is limited to qualitative information (i.e. high or low). The algorithm
does not provide a quantitative assessment of LAP. Independent of the algorithm, the guidelines
indicate that age is a consideration when assessing filling patterns, as a normal filling pattern for an
older patient may represent mild diastolic dysfunction for a younger patient.
From the point of view of the intensivist, we have concerns about the practical application of the
ASE/EACI algorithm. By definition, all aspects of the ACCE examination are performed and interpreted
for immediate application at the bedside by the intensivist (unlike consultative cardiology where the
examination is typically performed by a qualified echocardiography technician). Given the challenge of
time constraints, clinical pressure, and the high prevalence of patient specific factors that degrade image
acquisition, it is not practical for the intensivist to perform all parts of the ASE/EACI algorithm.
1. Left atrial volume measurement: Accurate measurement of LA volume requires application of
Simpson’s method using two on-axis orthogonal views of the LA with clear endomyocardial
visualization. While this is practical in the consultative echocardiography laboratory, it is not so
in the critically ill patient. Informally, we know of no ACCE expert who performs this
measurement on a regular basis. We recommend the intensivist performing ACCE not measure
the LA volume on a routine basis. Instead, it is appropriate to use M-mode measurements, with
understanding the limitations of the technique.
2. Tricuspid regurgitation velocity: While some degree of TR is commonly identified with color
Doppler, in only a proportion of cases will a well-defined continuous wave spectral Doppler
signal permit accurate measurement of peak systolic TR velocity. We agree that an attempt at
the measurement is always indicated, but observe that it may not always be feasible.
3. The algorithm recommends using the average of the lateral and septal mitral valve annular e’
velocity. This complicates the examination with unclear benefit. We recommend measuring
either the lateral or septal e’ velocity.
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4. Valsalva maneuver: Although not included in the algorithm, the guidelines review the utility of
the maneuver for assessment of LV diastolic function. Use of Valsalva maneuver is not relevant
to the critically ill patient given their inability to perform the maneuver.
A Simplified Approach
Lanspa et al studied 167 patients with severe sepsis and septic shock and assessed a variety of
echocardiographic parameters of diastolic function within the first 24 hours of critical illness and their
association with clinical outcomes.23
Using the 2009 ASE algorithm, the LV diastolic function of 35% of
the patients could be categorized unambiguously. The remaining 65% could not be categorized, often
due to discordant results. Left atrial volume index and deceleration time were not associated with
clinical outcomes. Septal e’ and E/e’ allowed unambiguous categorization of 87% of the patients with
correlation to clinical outcomes. Based upon statistical analysis of their data, the authors defined
diastolic dysfunction by septal e’ < 8 cm/sec and proposed categorization into grade I (E/e’ ≤ 8), grade II
(8 < E/e’ < 13), and grade III (E/e’ ≥ 13). While these findings need to be replicated and studied against
an invasive gold standard with the updated ASE guidelines, there is a body of literature supporting the
utility of e’ and E/e’ in the assessment of diastolic function. Gonzalez et al defined diastolic dysfunction
by an e’ < 10 cm/s and demonstrated a trend towards increased mortality with reduced lateral e’.11
Mourad et al defined diastolic dysfunction by an e’ ≤ 8 cm/s and demonstrated that this parameter was
an independent risk factor associated with intensive care unit mortality (OR 7.7).14
Ritzema et al
compared echocardiographic parameters to an implanted LAP monitor in 15 patients and found that
E/e’ could reliably detect increased LAP.30
They found that an E/e’ average ≥ 14, E/e’ septal ≥ 15, or E/e’
lateral ≥ 12 signified an LAP > 15mmHg with an area beneath the receiver-operator curve > 0.9. Sturgess
et al defined diastolic dysfunction using e’ < 9.6 cm/s and E/e’ > 15, finding that E/e’ was an
independent predictor of hospital survival in septic shock.9 In a study comparing echocardiography to
invasive conductance catheter measurements, Kasner et al reported that E/e’ > 8 was the best
echocardiographic parameter to detect diastolic dysfunction.21
None of these studies considered that LA
volume index was a useful parameter for the assessment of LV diastolic function.
With this body of evidence, it is reasonable for the intensivist to define the presence of diastolic
dysfunction based on an e’ and/or an E/e’ value. Precisely which cutoff value to use is difficult to
determine due to the sample size and heterogeneity of current studies.
It is inevitable that a proportion of ACCE assessments of diastolic function will be indeterminate. In
these circumstances, the intensivist incorporates lung ultrasonography into the assessment of cardiac
function. The presence of a normal aeration pattern on lung ultrasonography (lung sliding with A-lines)
indicates that the pulmonary artery occlusion pressure is < 18 mmHg.31
In the setting of an
indeterminate diastolic assessment by ACCE, this would effectively eliminate a significant elevation of
LAP.
Summary:
Competence in ACCE allows the intensivist to estimate LAP and to evaluate diastolic function. There are
two approaches to estimation of LAP using Doppler based measurements:
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1. The intensivist may apply the ASE/EACI algorithms with the understanding that the calculation
of LA volume is not practical and that the TR regurgitation jet velocity may be difficult to
measure in some patients. Due to these constraints, the estimation of LAP will be indeterminate
in some patients using the ASE/EACI algorithm.
2. The intensivist may use a simplified approach where the E/e’ ratio is utilized to estimate LAP,
values greater than 14 indicating an increasing probability of an elevated LAP.
There are two approaches to the identification and grading of diastolic function:
1. The intensivist may apply the ASE/EACI algorithm with the understanding that the calculation of
LA volume is not practical and that the TR regurgitation jet velocity may be difficult to measure
in some patients. Due to these constraints, identification and grading of diastolic function will be
indeterminate in some patients using the ASE/EACI algorithm.
2. The intensivist may use a simplified approach where the e’ and E/e’ is utilized to determine
whether the patient has diastolic dysfunction. Based upon current literature, it is reasonable to
conclude that the patient with e’ < 8 cm/s and/or E/e’ > 14 has diastolic dysfunction. It is not
clear that there is need to grade diastolic dysfunction, as the grade may have limited clinical
utility in the critical care arena. This simplified approach designates diastolic function in a binary
manner: either the patient has it, or the patient does not have it.
Supplement A provides four case examples for the assessment of diastolic function and compares the
ASE/EACI algorithm results to the simplified approach.
Some qualifications apply to these measurements:
1. The ASE/EACI Statement is based upon expert opinion, so the cutoff values used in the ASE/EACI
algorithm are reasonable but arbitrary.
2. The simplified approach is derived from several relevant studies in the critical care literature, so
the cutoff values are reasonable but arbitrary.
3. Doppler based assessment of diastolic function has not been well validated against invasive
measurements of diastolic function in critically ill patients.
4. The relevance of Doppler measurements of diastolic function to therapeutic intervention and
patient outcome are not well validated.
5. The intensivist is mindful of the specific limitations to measurement of annular velocities and
mitral inflow velocities that are used both in the ASE/EACI algorithms and the simplified
approach vide supra.
6. Numerical cutoff values may not be the best approach to estimating LAP. A “gray zone”
approach, similar to that proposed by Cannesson et al may be more appropriate.32
In this model,
the E/e’ ratio occurs along a continuum of probability. Rather than assigning a single arbitrary
value to define the presence of an elevated LAP, a given E/e’ would be associated with a
probability that the LAP is elevated.
7. Lung ultrasonography is a useful adjunct to Doppler measurements for evaluation of whether
respiratory failure is related to cardiogenic pulmonary edema or primary lung injury.33
Acknowledgements
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Guarantor statement: Yonatan Greenstein is the guarantor of the content of this manuscript and takes
full responsibility for the accuracy of its content including the data and analysis.
Author Contributions: All authors significantly contributed to all aspects of this manuscript.
Financial/nonfinancial disclosures: No authors have relevant disclosures pertaining this manuscript.
Tables
Table 1 - Types of Doppler
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Table 2 – Normative Values22
Figure Legends
Figure 1 – Diastolic Filling Curve
Figure 2A – 2016 ASE/EACI Algorithm for Evaluation of LV Diastolic Function in Patients with Normal Left
Ventricular Ejection Fraction
Figure 2B –2016 ASE/EACI Algorithm for Evaluation of LV Diastolic Function for Patients with Reduced
Left Ventricular Ejection Fraction
Figure 3 – Pulsed wave Doppler analysis of early and late diastolic filling
Figure 4 – Continuous wave Doppler demonstrating tricuspid regurgitation
Figure 5 – Tissue Doppler imaging of the lateral mitral valve annulus
Videos
Video 1 – Pulsed wave Doppler measurement of mitral inflow velocities
Video 2 – Tissue Doppler imaging measurement of the peak velocity of the lateral mitral valve annulus.
References
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1. Mayo PH, Beaulieu Y, Doelken P, et al. American College of Chest Physicians/La Societe De
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14. Mourad M, Chow-Chine L, Faucher M, et al. Early diastolic dysfunction is associated with
intensive care unit mortality in cancer patients presenting with septic shock. Br J Anaesth
2014;112(1):102-109.
15. Landesberg G, Jaffe AS, Gilon D, et al. Troponin elevation in severe sepsis and septic shock: The
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19. Ommen SR, Nishimura RA, Appleton CP, et al. Clinical utility of Doppler echocardiography and
tissue Doppler imaging in the estimation of left ventricular filling pressures. A comparative
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20. Combes A, Arnoult F, Trouillet JL. Tissue Doppler imaging estimation of pulmonary artery
occlusion pressure in ICU patients. Intensive Care Med 2004;30(1):75-81.
21. Kasner M, Westermann D, Steendijk P, et al. Utility of Doppler echocardiography and tissue
Doppler imaging in the estimation of diastolic function in heart failure with normal ejection
fraction. A comparative Doppler-conductance catheterization study. Circulation
2007;116(6):637-647.
22. Nagueh SF, Appleton CP, Gillebert TC, et al. Recommendations for the evaluation of left
ventricular diastolic function by echocardiography. J Am Soc Echocardiogr 2009;22(2):107-133.
23. Lanspa MJ, Gutsche AR, Wilson EL, et al. Application of a simplified definition of diastolic
function in severe sepsis and septic shock. Crit Care 2016;20(1):243.
24. Nagueh SF, Smiseth OA, Appleton CP, et al. Recommendations for the evaluation of left
ventricular diastolic function by echocardiography: An update from the American Society of
Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc
Echocardiogr 2016;29(4):277-314.
25. Otto CM. Textbook of Clinical Echocardiography, 5th
ed. Philadelphia, PA: Elsevier
Saunders;2013.
26. Oh JK, Seward JB, Tajik AJ. The Echo Manual, 3rd
ed. Philadelphia, PA: Lippincott Williams &
Wilkins;2006.
27. Nagueh SF, Middleton KJ, Kopelen HA, et al. Doppler tissue imaging: a noninvasive technique for
evaluation of left ventricular relaxation and estimation of filling pressures. J Am Coll Cardiol
1997;30(6):1527-1533.
28. Yalcin F, Kaftan A, Muderrisoglu H, et al. Is Doppler tissue velocity during early left ventricular
filling preload independent? Heart 2002;87(4):336-339.
29. Lang RM, Badano LP, Mor-Avi V, et al. Recommendations for cardiac chamber quantification by
echocardiography in adults: An update from the American Society of Echocardiography and the
European Association of Cardiovascular Imaging. Eur Heart J 2015;16(3):233-271.
30. Ritzema JL, Richards AM, Crozier IG, et al. Serial Doppler echocardiography and tissue Doppler
imaging in the detection of elevated directly measured left atrial pressure in ambulant subjects
with chronic heart failure. JACC Cardiovasc Imaging 2011;4(9):927-934.
31. Lichtenstein DA, Meziere GA, Lagoueyte JF, et al. A-ine and B-lines. Lung ultrasound as a bedside
tool for predicting pulmonary artery occlusion pressure in the critically ill. Chest
2009;136(4):1014-1020.
32. Cannesson M, Manach YL, Hofer CK. Assessing the diagnostic accuracy of pulse pressure
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33. Copetti R, Soldati G, Copetti P. Chest sonography: a useful tool to differentiate acute cardiogenic
pulmonary edema from acute respiratory distress syndrome. Cardiovasc Ultrasound 2008;6:16.
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Table 1 - Types of Doppler
Doppler Type Typical Applications Advantages Limitations
Continuous Wave
Doppler
Measurement of
velocities of
regurgitation and/or
stenosis
Able to measure high
blood flow velocity
measurements without
aliasing
Range ambiguity
Pulsed Wave Doppler Measure of low
velocities at a specific
location (i.e. LVOT VTI
for SV measurement)
Range resolution Unable to measure
high blood flow
velocities due to
aliasing
Color Flow Doppler Mapping of blood flow
velocities
2D flow information
superimposed on
ultrasonography image
Gain sensitive; flow
measured indirectly;
wall jets; aliasing with
high flow velocities
Tissue Doppler
Imaging
Measurement of
myocardial velocities
Ability to measure
myocardial velocities
Small velocity range
(low)
Legend: LVOT – left ventricular outflow tract; VTI – velocity time integral; SV – stroke volume; 2D – two-
dimensional
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Table 2 – Normative values for young, healthy individuals22,25
Measurement Normative Range
Peak E wave velocity 0.6 – 0.8 m/s
Peak A wave velocity 0.19 – 0.35 m/s
E/A 1.32
Septal e’ 10 – 15 cm/s
Lateral e’ 12.9 – 20.6 cm/s
E/e’ < 8
Legend: m/s – meters per second
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Figure 2A – 2016 ASE/EACI Algorithm for Evaluation of LV Diastolic Function in Patients with Normal Left
Ventricular Ejection Fraction
LVEF – left ventricular ejection fraction; TR – tricuspid regurgitation; LA – left atrium
Normal LVEF
(1) Average E/e' > 14
(2) Septal e' velocity < 7 cm/s or lateral e' velocity < 10 cm/s
(3) TR velocity > 2.8 m/s
(4) LA volume index > 34 mL/m2
Normal diastolic
function Indeterminate Diastolic
dysfunction
50% positive <50% positive >50% positive
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Figure 2B – 2016 ASE/EACI Algorithm for Evaluation of LV Diastolic Function for Patients with Reduced
Left Ventricular Ejection Fraction
TR – tricuspid regurgitation; LA – left atrium, LAP – left atrial pressure
When only 2 criteria are available
E/A ≤ 0.8 + E ≤ 50
cm/s
Mitral Inflow
E/A ≤ 0.8 + E > 50
m/s
Or
E/A > 0.8 - <2
E/A ≥ 2
3 criteria to be evaluated*
(1) Average E/e’ > 14
(2) TR velocity > 2.8 m/s
(3) LA volume index > 34 mL/m2
2 of 3 or 3 of
3 negative
2 of 3 or 3 of
3 positive
2 negative 1 positive and 1
negative 2 positive
Normal LAP
Grade I diastolic
dysfunction
Indeterminate LAP
and diastolic
dysfunction grade
Increased LAP
Grade II diastolic
dysfunction
Increase LAP
Grade III diastolic
dysfunction
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e-Appendix 1. Case examples for the assessment of diastolic function
Case #1
These images were recorded from a 70-year-old female with reduced left ventricular (LV) function using transthoracic echocardiography (TTE). Although the patient was in sinus rhythm, there was no detectable A wave. A peak tricuspid regurgitation (TR) jet velocity could not be obtained, and there was no left atrial (LA) volume measurement. E wave velocity is 99.8 cm/sec, e’ is 6.3 cm/sec, and E/e’ is 15.8.
Case 1 – Pulsed wave Doppler measurement of mitral valve inflow
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Case 1 - Tissue Doppler imaging of lateral mitral valve annulus
Case #1
Evaluation of LV diastolic function
By ASE/EACI algorithm:
Referring to figure 2B and lacking a measurable A wave, TR velocity, or LA volume measurement; the patient is classified with indeterminate diastolic function.
By simplified approach:
The finding of an e’ < 8 is consistent with the presence of diastolic dysfunction. The finding of an E/e’ > 14 is consistent with the presence of diastolic dysfunction. The simplified approach does not further classify the degree of diastolic dysfunction (as would the ASE/EACI algorithm).
Estimation of LA pressure (LAP)
By ASE/EACI algorithm:
Referring to figure 2B and lacking a measurable A wave, TR velocity, or LA volume measurement, it is not possible to estimate LAP.
By simplified approach:
The E/e’ is greater than 14, so the patient has an elevation of LAP.
Comment: Without measurement of LA volume index or peak TR jet velocity, the ASE/EACI algorithm yields an indeterminate result. The simplified approach permits evaluation of LAP.
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Case #2
These images were recorded from a 62-year-old male with reduced LV function. The measurements were recorded using transesophageal echocardiography (TEE) from the mid-esophageal four chamber view. A peak TR jet velocity could not be obtained, and there was no LA volume measurement. E wave velocity is 96.2 cm/sec, A wave velocity is 58.6 cm/sec, E/A is 1.64, e’ is 14.1 cm/sec, and E/e’ is 6.8.
Case 2 – Pulsed wave Doppler measurement of mitral valve inflow
Case 2 – Tissue Doppler imaging of lateral mitral valve annulus
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Case #2
Evaluation of LV diastolic function
By ASE/EACI algorithm:
Referring to figure 2B, the E wave velocity and E/A ratio by themselves do not allow classification of diastolic function. Lacking a measurable peak TR velocity or LA volume measurement; the patient is classified with indeterminate diastolic function.
By simplified approach:
The finding of a e’ > 8 cm/sec indicates normal diastolic function. The finding of an E/e’ < 14 indicates normal diastolic function.
Estimation of LAP
By ASE/EACI algorithm
Referring to figure 2B , the E wave velocity and E/A ratio by themselves do not allow estimation of LAP. Lacking a peak TR velocity, or LA volume measurement, it is not possible to estimate LAP.
By simplified approach
The low E/e’ ratio indicates that there is no elevation of LAP.
Comment: It is unusual to measure a normal e’ velocity with co-existent reduction of LV function. This remains unexplained in this case. Without measurement of LA volume index or peak TR jet velocity, the ASE/EACI algorithm yields an indeterminate result. The simplified approach permits evaluation of diastolic function and LAP.
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Case #3
These images were recorded from a 70-year-old female with normal LV function using TTE. A peak TR jet velocity could not be obtained, and there was no LA volume measurement. E wave velocity is 55.3 cm/sec, A wave velocity is 81.8 cm/sec, E/A is 0.68, e’ is 6.1 cm/sec, and E/e’ is 9.1.
Case 3 – Pulsed wave Doppler measurement of mitral valve inflow
Case 3 – Tissue Doppler imaging of lateral mitral valve annulus
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Case #3
Evaluation of LV diastolic function
By ASE/EACI algorithm:
Referring to figure 2A, the e’ and E/e’ by themselves do not allow categorization of diastolic function. Lacking TR velocity or LA volume measurement; the patient is classified with indeterminate diastolic function.
By simplified approach:
The finding of a e’ < 8cm/sec indicates abnormal diastolic function. The finding of an E/e’ < 14 does not support diastolic dysfunction. The simplified approach allows an and/or approach whereby the presence of either the e’ < 8 cm/sec and/or E/e’ > 14 is consistent with diastolic dysfunction. The “grey zone” approach further holds that the probability of diastolic dysfunction is increased when both values are consistent.
Estimation of LAP
By ASE/EACI algorithm
Referring to figure 2B, the E wave velocity and E/A ratio by themselves do not allow estimation of LAP. Lacking a peak TR velocity or LA volume measurement, it is not possible to estimate LAP.
By simplified approach
The low E/e’ ratio indicates that there is no elevation of LAP.
Comment: Without measurement of LA volume index or peak TR jet velocity, the ASE/EACI algorithm yields an indeterminate result. The simplified approach permits evaluation of diastolic function and LAP. This case is another example of the difficulty of using the ASE/EACI algorithm in the critically ill patient. Patient specific factors, the physical challenge of properly positioning the patient, respirophasic translational artifact, and time constraints all combine to make it difficult to measure LA volume index or obtain good quality peak TR velocity on a routine basis.
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Case #4
These images were recorded from an 80-year-old male with normal LV function using TTE. There was no LA volume measurement. E wave velocity is 64.6 cm/sec, A wave velocity is 43.5 cm/sec, E/A is 1.5, e’ is 4.7 cm/sec, E/e’ is 13.7, and peak TR jet velocity is 2.03 m/sec.
Case 4 - Pulsed wave Doppler measurement of mitral valve inflow
Figure 6 - Case 3 – Tissue Doppler imaging of lateral mitral valve annulus
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Case 4 – Continuous wave Doppler measurement of peak tricuspid regurgitation jet velocity from the apical four chamber view
Case #4 Interpretation
Evaluation of LV diastolic function
By ASE/EACI algorithm:
Referring to figure 2A, the e’, E/e’, and TR jet velocity by themselves do not allow categorization of diastolic function. Lacking a LA volume index the patient is classified with indeterminate diastolic function.
By simplified approach:
The finding of a e’ < 8 cm/sec indicates abnormal diastolic function. The finding of an E/e’ is < 14 does not support diastolic dysfunction. The simplified approach allows an and/or approach whereby the presence of either the e’ < 8 cm/sec and/or E/e’ > 14 is consistent with diastolic dysfunction. The grey zone approach further holds that the probability diastolic dysfunction is increased when both values are consistent.
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Estimation of LAP
By ASE/EACI algorithm
Referring to figure 2B, the E wave velocity and E/A ratio by themselves do not allow estimation of LAP. The TR velocity is not consistent with elevated LAP. Together, these measurements are consistent with normal LAP.
By simplified approach
The E/e’ < 14 indicates that that there is no elevation of LAP.
Comment: This case is complicated by the presence of severe RV dilation (seen on the TTE examination and confirmed by the small image shown with the Doppler tracing). As the right atrial pressure was 20mm Hg in this case, the peak TR velocity of 2.03 m/sec indicates that the patient has an elevation of pulmonary systolic artery pressure. The arbitrary cutoff of 2.8 m/sec used in the ASE/EACI algorithm was selected as a means of ruling out pulmonary arterial hypertension. While this is an useful screening approach in the patient that has normal right atrial pressure, it does not take into account the patient with high right atrial pressure. Severe RV enlargement is typically associated with a reduction in E wave velocity due to interventricular dependence, so there is a possibility that the measured E wave velocity (and therefore E/e’ ratio) are false negative values. This emphasizes the need to interpret standard indices of diastolic function in the context of the entire echocardiography examination.
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